This is a submission of a new program project grant to the NHLBI by four investigators located within the College of Medicine of the Pennsylvania State University in Hershey, Pennsylvania. All investigators have NIH R01 funded programs and all have been highly productive scientists. All project leaders are collaborative and all will greatly benefit from this program. We believe this application fulfills the criteria for a PPG because: 1) there is a unifying theme which is neural control of the circulation; 2) there are conceptual synergies between the various projects that will lead to results that elucidate important issues of cardiovascular physiology and pathophysiology; 3) this proposal has broadly defined goals that can be accomplished within the first 5 year funding period; and 4) many of the ideas and concepts proposed in this application are a direct result of previous collaborations between the project leaders. Dr. Lawrence Sinoway will be the Program Director of this application. He has outstanding scientific, administrative experience. He has been the Program Director the Penn State University General Clinical Research Center (GCRC) since 1996. In this capacity, he led a successful renewal application effort in 1999 as well as a successful effort to obtain an NIH construction grant to renovate the GCRC (funded in 2001). In Project 1, Dr. Sinoway will examine afferent and efferent components of the exercise pressor reflex in human subjects. In Project 2, Dr. Urs Leuenberger will examine the neurovascular responses to systemic hypoxia in human subjects. In Project 3, Dr. Hui-lin Pan will use the paraventricular nucleus (PVN) of the hypothalamus to better understand mechanisms of central sympathetic, synaptic transmission in conditions associated with heightened sympathetic tone (i.e. hypertension). In Project 4, Dr. Chester Ray will examine the vestibulosympathetic reflex in individuals with reduced sympathetic outflow (exercise conditioned subjects and those with idiopathic orthostatic intolerance). Core Laboratory B will be a physiology core. All projects will use this core.